Problems in predicting cell damage from bubble bursting

Dey, Debadeepta; Emery, A. N.

doi:10.1002/(sici)1097-0290(19991020)65:2<240::aid-bit16>3.0.co;2-p

Cited by 13 publications

(1 citation statement)

References 12 publications

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“…More importantly, bubble formation at the sparger and bubble rupture at the liquid surface are known to be the major cause for cell death by hydrodynamic forces in these processes [44-46]. Attachment of cells to bubbles plays an important role in the lethal effects of bursting bubbles in cell culture processes [47,48]. There is no evidence that these effects may have an influence on the maximum stable drop size.…”

Section: Resultsmentioning

confidence: 99%

Characterization of hydromechanical stress in aerated stirred tanks up to 40 m3 scale by measurement of maximum stable drop size

et al. 2014

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BackgroundTurbulence intensity, or hydromechanical stress, is a parameter that influences a broad range of processes in the fields of chemical engineering and biotechnology. Fermentation processes are often characterized by high agitation and aeration intensity resulting in high gas void fractions of up to 20% in large scale reactors. Very little experimental data on hydromechanical stress for such operating conditions exists because of the problems associated with measuring hydromechanical stress under aeration and intense agitation.ResultsAn indirect method to quantify hydromechanical stress for aerated operating conditions by the measurement of maximum stable drop size in a break-up controlled dispersion was applied to characterize hydromechanical stress in reactor scales of 50 L, 3 m3 and 40 m3 volume with a broad range of operating conditions and impeller geometries (Rushton turbines). Results for impellers within each scale for the ratio of maximum to specific energy dissipation rate ϕ based on measured values of maximum stable drop size for aerated operating conditions are qualitatively in agreement with results from literature correlations for unaerated operating conditions. Comparison of data in the different scales shows that there is a scale effect that results in higher values for ϕ in larger reactors. This behavior is not covered by the classic theory of turbulent drop dispersion but is in good agreement with the theory of turbulence intermittency. The data for all impeller configurations and all aeration rates for the three scales can be correlated within ±20% when calculated values for ϕ based on the measured values for dmax are used to calculate the maximum local energy dissipation rate. A correlation of the data for all scales and all impeller configurations in the form ϕ = 2.3∙(ϕunaerated)0.34∙(DR)0.543 is suggested that successfully models the influence of scale and impeller geometry on ϕ for aerated operating conditions.ConclusionsThe results show that besides the impeller geometry, also aeration and scale strongly influence hydromechanical stress. Incorporating these effects is beneficial for a successful scale up or scale down of this parameter. This can be done by applying the suggested correlation or by measuring hydromechanical stress with the experimental method used in this study.

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Section: Resultsmentioning

confidence: 99%

Characterization of hydromechanical stress in aerated stirred tanks up to 40 m3 scale by measurement of maximum stable drop size

et al. 2014

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Bioreactors, Cell Culture, Commercial Production

Zhou

et al. 2010

Encyclopedia of Industrial Biotechnology

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Various recombinant proteins expressed by animal cells and secondary metabolites produced by plant cells have significantly increased the demand for high‐value‐added (mainly biopharmaceutical) products in recent years. Without doubt, large‐scale efficient production of these compounds is very important to meet market requirements. As animal cells and plant cells are more sensitive to culture conditions than microorganisms, their bioreactor culture technique is critical to reduce the production cost. In order to favor the desired functions of the cells and achieve cost‐effective large‐scale manufacture, it is necessary to optimize and control the bioreactor environment via operating variables. In this article, the characteristics of various types of cell culture bioreactors including stirred‐tank bioreactors, pneumatically agitated bioreactors, membrane bioreactors, packed and fluidized‐bed bioreactors, and wave bioreactors are discussed. Details of basic bioreactor design principles such as shear force, oxygen supply, and mixing are introduced. The effects of process variables including oxygen and mass transfer, fluid mixing, temperature, pH, and light irradiation on cell cultures are described. Bioreactor operation strategies for cell cultures are compared. For commercial production scale‐up, different criteria are considered and industrial large‐scale examples are also illustrated.

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Large‐scale propagation of a replication‐defective adenovirus vector in stirred‐tank bioreactor PER.C6™ cell culture under sparging conditions

Xie¹,

Metallo²,

Warren³

et al. 2003

Biotech & Bioengineering

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Large-scale propagation of replication-defective adenovirus vectors has not been well studied to date. One of the challenges for efficient propagation at large scale is to overcome the sensitivity of virus infected cells to gas sparging required for oxygenation and CO(2) removal. In our initial experiments, it was observed that productivity of an adenovirus vector was significantly reduced under sparging conditions as compared to nonsparged, i.e., surface-aerated controls in serum-free cultures. Investigations led to the identification of a buffer containing surfactant (Polysorbate-80, PS-80) that was included in the virus seed stock formulation and introduced through virus infection into the culture at a very low concentration as the cause of the reduced virus productivity. This finding was not obvious and trivial, as neither uninfected sparged nor infected nonsparged PER.C6 trade mark cells in serum-free cultures were affected by the buffer at such a low PS-80 concentration of 0.00025% (v/v), which is a common component of serum-free cell culture media. These results strongly suggest that virus-infected cells behave very differently from uninfected cells under sparging conditions. To mitigate the deleterious effects of sparging, the virus seed stock was prepared in the absence of the buffer containing PS-80. At the same time, the concentration of Pluronic-F68 (PF-68) in the serum-free medium was increased to 1 g/L, at which cell growth and metabolism were unaffected, even though this measure alone did not result in virus productivity improvement. Only by implementing the two measures together was virus productivity loss completely eliminated under sparging conditions. After demonstration of the process robustness in 2-L bioreactors, this adenovirus propagation process was successfully scaled up to 250 L in a 300-L bioreactor under the worst-case sparging conditions projected for 10,000-L scale.

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Problems in predicting cell damage from bubble bursting

Cited by 13 publications

References 12 publications

Characterization of hydromechanical stress in aerated stirred tanks up to 40 m3 scale by measurement of maximum stable drop size

Characterization of hydromechanical stress in aerated stirred tanks up to 40 m3 scale by measurement of maximum stable drop size

Bioreactors, Cell Culture, Commercial Production

Large‐scale propagation of a replication‐defective adenovirus vector in stirred‐tank bioreactor PER.C6™ cell culture under sparging conditions

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